Anti-CD45 radioimmunotherapy using 211At with bone marrow transplantation prolongs survival in a disseminated murine leukemia model

Despite aggressive chemotherapy combined with hematopoietic stem cell transplantation (HSCT), many patients with acute myeloid leukemia (AML) relapse. Radioimmunotherapy (RIT) using monoclonal antibodies labeled with beta-emitting radionuclides has been explored to reduce relapse. beta emitters are limited by lower energies and nonspecific cytotoxicity from longer path lengths compared with a emitters such as At-211, which has a higher energy profile and shorter path length. We evaluated the efficacy and toxicity of anti-CD45 RIT using At-211-anti-CD45 At in a disseminated murine AML model. Biodistribution studies in leukemic SJL/J mice showed excellent localization of At-211-anti-CD45 At-anti-murine CD45 mAb (30F11) to marrow and spleen within 24 hours (18% and 79% injected dose per gram of tissue [ID/g], respectively), with lower kidney and lung uptake (8.4% and 14% ID/g, respectively). In syngeneic HSCT studies, At-211-anti-CD45 At-B10-30F11 RIT improved the median survival of leukemic mice in a dose-dependent fashion (123, 101, 61, and 37 days given 24, 20, 12, and 0 mu Ci, respectively). This approach had minimal toxicity with nadir white blood cell counts >2.7 K/mL 2 weeks after HSCT and recovery by 4 weeks. These data suggest that At-211-anti-CD45 RIT in conjunction with HSCT may be a promising therapeutic option for AML.